Local Research, Global Impact

For some people, an allergy is a lot more serious than a
runny nose; their allergies can literally kill them. Anaphylaxis is
a whole-body, rapid-onset, life-threatening allergic reaction.
There are approximately 1,500 deaths in the U.S. every year due to
anaphylaxis. Symptoms may include breaking out in hives or a rash,
a swollen tongue or throat, trouble breathing, wheezing, and even
respiratory arrest.

Because of the potential consequences, St. Louis allergist
Dr. Ray Davis, professor of clinical pediatrics at Washington
University School of Medicine, is a member of the national
Anaphylaxis Community Experts (ACE). “Food allergies in particular
have become epidemic in this country. Our problem is not being able
to predict if a known allergen will cause anaphylaxis,” he says. “A
rash with last exposure could lead to respiratory arrest with the
next one. We want families and schools to be prepared to act
quickly.”

Davis says the first line of therapy is using an EpiPen, a
pre-loaded automatic syringe containing epinephrine, along with
prompt 911 help. Don’t try to get your child to the ER. Administer
the epinephrine as soon as any symptoms occur, and have paramedics
come to you. The most frequent triggers are drugs, bee stings and
food allergies such as peanuts, but any food can do it in a
susceptible person. ACE’s goal is to prepare parents and schools to
have a response plan: know the suspect foods, let everyone else
know, recognize the symptoms, and respond quickly with an EpiPen
and by calling 911.

If you suspect your child has a food allergy, get him
tested. Chances of dying from anaphylaxis are increased with
exposure to the allergen, the presence or history of asthma
symptoms, and delay in giving epinephrine. One child had an allergy
to milk, resulting in a rash. A year later, his mother accidently
used real milk in a muffin mix. He got a rash and she didn’t use
the EpiPen. He was rushed to the ER in shock, where he was given
epinephrine and fluids, but still died, Davis relates. “You have to
administer it at the first sign of any allergic reaction.” Helpful
websites include: http://aanma.org/anphylaxis">aanma.org/anphylaxis, where forms
can be downloaded to fill out and take to school, and http://acaai.org">acaai.org, the American College of Allergy,
Asthma & Immunology.

Compression-Only
CPR

Heart attack patients without a heartbeat do better when lay
bystanders perform only chest compression rather than chest
compression and rescue breathing, according to an analysis at
Washington University School of Medicine. Dr. Peter Nagele, the
lead investigator and chief of trauma anesthesiology at
Barnes-Jewish Hospital, took data from three studies to determine
the survival benefit.

The studies looked at bystanders who called 911 and were
instructed by the dispatcher to do chest compression-only CPR.
Their proficiency in CPR had no impact because it was relatively
simple for a bystander to find the proper area on the chest and
keep doing compressions until medical assistance arrived.

Nagele says that even though a well-coordinated effort of
rescue breathing and chest compression is the gold standard, if EMS
can respond quickly, compressions can mean the difference between
life and death. “Only one-third of bystanders to an arrest do
anything,” he notes. “If they call 911 and are coached to do
compression-only CPR they can be a bridge to survival. It depends
on the likelihood of quick EMS or defibrillator response. Ten to 15
minutes without CPR gives the person no chance of survival. Call
911 and do something. If it’s a witnessed arrest, start
compressions immediately. Have someone else call 911 and send
someone for an automated external defibrillator (AED) if it’s
available, but keep doing compressions. When EMS can respond
quickly, compression-only can bridge the gap. At some point,
everyone needs oxygen.”

Arrests in children or drownings are different. Oxygen
is much more critical, so rescue breathing should be included.
Nagele says it is rare for kids to go into cardiac arrest from a
primary heart problem. It is more likely to be secondary to a
severe asthma attack, an allergic reaction or something else
unrelated to the heart. Those situations call for oxygen. He
strongly recommends chest compression and rescue breaths in kids,
or rescue breathing alone where a pulse is present but the person
isn’t breathing.

Low Testosterone &
Alzheimer’s

A recent study of 153 Chinese men demonstrated that low
testosterone was an independent risk factor for the development of
Alzheimer’s disease in older men. When the study started, the men,
who were 55 or older didn’t have dementia, but most had some mild
memory loss. Within a year, 10 of those with memory loss developed
probable Alzheimer’s disease. When tested, they also had low
testosterone in their body tissues. Dr. John Morley, one of the
study investigators and director of geriatric medicine at Saint
Louis University, was excited about the finding. “Ten years ago we
had a mice model with low testosterone and Alzheimer’s symptoms.
When we gave them supplemental testosterone, it blocked the beta
amyloid production and they got better,” Morley notes. “In the Hong
Kong study, those patients with low testosterone went on to develop
Alzheimer’s much faster, within a year. Low levels of this hormone
seem to allow beta amyloid, the plaque found in the brains of
Alzheimer’s patients, to proliferate.”

The Hong Kong findings were consistent with finding in other
small studies of older Caucasian men. The next step, says Morley,
is to conduct a large-scale study to investigate the use of
testosterone in preventing Alzheimer’s disease. At this point, he
doesn’t want people running to their doctor to get it. “They need
to have symptoms of low testosterone, such as decreased libido or
impotence, before we’d test for it. Then if it’s low we would
prescribe it for those symptoms. We still need to do larger studies
to find out if it’s logical to give testosterone supplements to
prevent dementia, and to determine what the long-term effects might
be.”

Neurofibromatosis 1 &
ADD

One in 3,000 children are born with an inherited condition
called neurofibromatosis1 (NF1), a tumor disorder caused by the
malfunction of a gene on chromosome 17 responsible for cell
division. That’s more than cystic fibrosis and muscular dystrophy
combined. Those with the disorder can have multiple symptoms:
non-cancerous lumps, scoliosis (curvature of the spine), eye
problems and even epilepsy. One in five NF1 children develops brain
tumors. A recent mouse study at Washington University School of
Medicine discovered that NF1 can also impair development of the
brain system that facilitates attention, which helps explain why
ADD and learning disabilities are sometimes seen in these
children.

Dr. David Gutmann, professor of neurology at Washington
University and director of the NF Center, says that they were able
to restore normal attention levels with Ritalin. He finds the
significance of this startling. “Two-thirds of kids with NF1 have
attention problems and a wide spectrum of learning problems. The
majority are attention-deficit, but without hyperactivity. There
has been reluctance on the part of parents to use Ritalin. This
study demonstrated in a mouse model exactly how Ritalin works to
help this problem, by affecting dopamine levels. In NF mice with
attention deficit, dopamine levels were very low. We gave them
Ritalin and improved attention by increasing dopamine. It’s a good
example of how mouse models help us make sense of why certain drugs
work in people.”

Adults diagnosed with ulcerative colitis after age 50 are
more likely to achieve remission than patients diagnosed at younger
ages, even with the same or similar treatments. Dr. Matthew Ciorba,
assistant professor of medicine in gastroenterology at Washington
University School of Medicine, was lead investigator and says that
younger people diagnosed with ulcerative colitis are more likely to
have a genetic component. “We think those people diagnosed after
age 50 have had changes in their immune system or are reacting to
environmental exposures,” he says.

Nearly 1 million Americans have ulcerative colitis, an
inflammation in the lining of the large intestine leading to
abdominal cramping in conjunction with chronic loose stools,
frequent diarrhea and sometimes blood in the stool. Treatment
starts with relatively mild maintenance drugs related to aspirin
(mesalamine) that reduce inflammation in the colon. For more severe
cases, immunosuppressants help control diarrhea. Extreme cases may
require removal of the colon.

Ciorba says diagnosed cases peak in late teens and early
twenties; then again in people over 50. Other studies have shown
that after 50, the immune system tends to quiet down somewhat, so
that might explain the better response to medications. The current
study involved 295 people treated at W.U. School of Medicine
between 2001 and 2008. After treatment, 64 percent of patients
diagnosed after age 50 were in remission, compared to 49 percent of
younger patients.

“Younger patients should not be distressed over this
finding. The message is that when you have persistent ulcerative
colitis symptoms, seek treatment early. It’s easier to treat before
it becomes severe and chronic. It’s also important to know that
this is an area of very active research, and new treatment
indicators are emerging all the time,” Ciorba says. His team says
more research is needed into the environmental and genetic factors
that differentiate when the disease arises to determine at what age
patients respond to different therapies. Repeat UTIs

Fifteen million cases of urinary tract infections (UTIs)
annually drive women to their doctors and cost $1.6 billion to
diagnose and treat. The most effective treatment currently is
antibiotics, but in 10 percent of women, as soon as the antibiotics
are gone, another UTI starts up. Researcher Scott Hultgren,
director of the Center for Women’s Infectious Disease Research at
Washington University School of Medicine, reports on what the
research has shown. “Using a mouse model, we have found that when
the immune system overreacts to a UTI, it tends to recur. If the
initial infection hangs on long enough to cause bladder damage,
then those changes in the bladder walls make later infection more
likely.”

Hultgren says it’s important to know why this happens so
they can intervene and come up with novel therapies, preferably not
antibiotics. E. coli is the most common bacterium involved in these
infections, he says, and secretes a glue that helps it gradually
invade the bladder walls. “Right now the No. 1 antibiotic for
bladder infections is a fluoroquinalone like Cipro, and resistance
is on the rise. We’re reaching a tipping point of running out of
antibiotics that will work,” he says. Their research, vitally
important in dissecting the details of how these bacteria interact
with the host, has led to a multi-pronged approach. One prong is a
possible vaccine against adhesion of the bacteria so they get
flushed out and can alert the immune system that a foreign invader
is present.

Another approach is to research the glue itself. The bladder
is coated with a sugar called mannose. E. coli has developed the
ability to specifically recognize that sugar and bind to it. “We’re
now working with chemists to design sugars that are soluble and
will bind 1,000 times tighter than mannose, filling the binding
space and shutting out the connections for the E. coli. We just
finished a mouse study where we gave this preparation orally and it
worked,” says Hultgren.

The third approach has been to address the adhesions on the
tips of hair-like fibers (pili) on the E. coli. They are developing
a pilacide to prevent these fibers from growing. Hultgren says all
these approaches are designed to prevent the infection cycle and
would initially be given to women with a history of three or more
UTIs a year. Later, they may be used as therapy in lieu of
antibiotics.

Soy &
Asthma

A recent clinical study showed that in people with asthma,
the ones who ate the least soy had the most flare-ups. Another
pilot study showed patients on soy had increased lung function and
decreased hyper-responsiveness to asthma triggers. Based on what we
know about soy, a large clinical trial involving 19 sites will
compare asthma attacks between a placebo group and a group that
consumes two capsules of soy isoflavones a day. Dr. Mario Castro, a
lung specialist at Barnes-Jewish Hospital and lead investigator for
the W.U. study site for Soy Isoflavones in Asthma (SOYA) study,
says the asthma rate in the U.S. has increased to 12 percent in
recent years. One reason for that increase might be our decreased
consumption of food rich in antioxidants, like soy.

Isoflavones are powerful antioxidants found in soy products
like tofu and edamame, as well as in other types of beans, alfalfa
sprouts and lentils. They have been linked to lowered risks of
heart disease, osteoporosis and even some cancers. They have been
shown to slow inflammation, a component in asthma symptoms.
However, Castro says, you would have to consume a lot of these
foods to get the antioxidant effect contained in two daily
capsules.

Nationwide the study will enroll 380 patients 12 years and
older who are taking either inhaled corticosteroids or a
leukotriene modifier such as Singulair, and who still have some
uncontrolled asthma symptoms.

Castro says the beauty of this trial is that the product
being used with the test group is Novasoy, already on the market as
50-milligram capsules. Study participants not in the control group
will take two of those capsules a day. “The product is freely
available and inexpensive, a potentially great alternative to
drugs,” Castro says.

Siblings of Autistic
Children

Brothers and sisters of children with autism have more
language delays and other subtle characteristics of autism than
previously thought. A new study by researchers at Washington
University School of Medicine found traits in siblings more
pronounced than in the general population. Dr. John Constantino,
first author and the director of child and adolescent psychiatry at
Washington University, says their findings indicate that it’s
possible additional children in the family are affected in some
degree by the same genes that contribute to autism in their
siblings.

The study found that one in five siblings thought to be
unaffected actually had language delays or speech problems early in
life. They also noticed that many of the girl siblings had subtle
traits, but few had a diagnosis of autism. In some families,
Constantino says, they saw a spectrum of symptoms across family
members. “It’s hard to put a cut-off on where autism begins, but we
find that symptoms occur much more frequently in affected families
than in the general population. We know autism is genetic but have
located only one gene that accounts for 10 percent of cases.”
Constantino says they don’t know if autism is due to a single gene
or multiple genetic factors. If many factors have to be present,
could they target one of them early in development and derail the
condition?

They also found that the genetic influences for autism cross
over into other conditions like ADHD and Tourette’s syndrome. Mild
symptoms in females might indicate carrier status. “Because
children with full-blown autism seldom have offpsring, there are
clear implications for offspring of people with these mild
symptoms. If we watch them closely as babies, we can intervene
quickly and early, and perhaps have better outcomes. Another
question yet to answer, Constantino notes, is, If siblings have a
susceptibility to autism what kept them from developing it? ¤